Clinical Research on Shenfu Injection in Septic Patients

Improving Microcirculation and Microvascular Leakage in Sepsis Patients: A Comprehensive Clinical Study of Shenfu Injection

Sepsis, characterized by organ dysfunction caused by infection, exhibits increasing incidence and mortality rates, posing a significant challenge to intensive care units. Early-stage sepsis involves hemodynamic disturbances, and severe and complex microcirculatory impairments can result in tissue hypoxia and accelerate organ dysfunction. Modern medical research has indicated that the effective and rapid restoration of microcirculatory function, along with the correction of microcirculatory disorders, is a crucial aspect in the treatment of sepsis. Current guidelines recommend the use of vasoactive drugs to address hemodynamic disturbances, but their administration may further damage the microcirculation. Additionally, in patients with severe sepsis, there often exists a disparity between macrocirculatory and microcirculatory hemodynamics, and conventional clinical indicators fail to directly reflect the level of microcirculatory perfusion.

Chinese guidelines have incorporated the use of traditional Chinese medicine (TCM) in the diagnosis and treatment of sepsis, offering a new therapeutic approach to ameliorate microcirculatory impairments. This study aims to include patients with sepsis and administer Shenfu Injection via intravenous therapy. Tongue microcirculation assessment will be employed to evaluate changes in microvascular health scores, while transcutaneous oxygen and carbon dioxide pressure alterations, as well as serum lactate level variations, will be monitored to ascertain the effects of Shenfu Injection on improving early-stage microcirculatory impairments and microvascular leakage in sepsis patients. This research will clarify the clinical efficacy of Shenfu Injection in sepsis patients with microcirculatory impairments, provide evidence-based medicine and clinical evidence for TCM treatment of sepsis, and offer a solid foundation for refining sepsis treatment strategies with distinct Chinese characteristics.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: Shen-Fu; Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongping Qu, phD,MD; Phone Number: +86 13641801889; Email: hongpingqu0412@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital
      • Contact: Jieming Qu, MD; Phone Number: +86 02164370045

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Signed informed consent form;
• Meets sepsis 3.0 diagnostic criteria;

Exclusion Criteria:

• Age < 18 years;
• Known pregnancy;
• Inability to accept and complete signed informed consent within 24 hours of diagnosis of sepsis;
• Status of tracheal intubation;
• oral mucosal inflammation or damage;
• Patients with contraindications to transcutaneous oxygen partial pressure testing such as severe edema and burns;
• Concurrent participation in other treatment studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Shenfu Injection group; within 24 hours after the diagnosis of sepsis, Shenfu injection 100 ml/day, intravenous use, continuous application for 7 days.	Drug: Shen-Fu; Within 24 hours of sepsis diagnosis, patients received a daily intravenous infusion of 100 ml of Shenfu Injection for a continuous duration of 7 days.; Other Names: Traditional Chinese medicine
Placebo Comparator: Control group; sepsis was treated with standardized western medicine methods	Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation; empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload; Other Names: Strandard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HR:heart rate	heart rate	Day0，Day1，Day 3，Day 7
BP:Blood pressure	Blood pressure	Day0，Day1，Day 3，Day 7
Proportion of perfused vessels	Grid-based score (3 horizontal and vertical equidistant lines). Percentage of perfused vessels per total number of vessel crossings	Day0，Day1，Day 3，Day 7
Microvascular fow index	fow, 1 = intermittent fow, 2 = sluggish fow, 3 = normal fow Semi-quantitative assessment of the average red blood cell velocity per quadrant	Day0，Day1，Day 3，Day 7
Heterogeneity index	Determinant of heterogeneity of blood fow, characteristic of distributive abnormalities	Day0，Day1，Day 3，Day 7
Hemodynamic parameters1	CI: Cardio index	Day0，Day1，Day 3，Day 7
Hemodynamic parameters2	SVRI:systemic vascular resistance index	Day0，Day1，Day 3，Day 7
Hemodynamic parameters3	GEDVI:global end-diastolic volume index	Day0，Day1，Day 3，Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ang2:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
VCAM1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
Sydecan-1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
6-Keto-PGF-1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
TXB2:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
NO:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0，Day1，Day 3，Day 7
Lab test1	PH	Day0，Day1，Day 3，Day 7
Lab test2	PaO2 mmHg,	Day0，Day1，Day 3，Day 7
Lab test3	PaCO2 mmHg	Day0，Day1，Day 3，Day 7
Lab test4	Serum lactate mmol/L	Day0，Day1，Day 3，Day 7
Lab test5	IL-10 ng/ml	Day0，Day1，Day 3，Day 7
Lab test6	WBC ×109/L	Day0，Day1，Day 3，Day 7
Lab test7	Neu ×109/L	Day0，Day1，Day 3，Day 7
Lab test8	Lym×109/L,	Day0，Day1，Day 3，Day 7
Lab test9	Hb g/L,	Day0，Day1，Day 3，Day 7
Lab test10	PLT×109/L	Day0，Day1，Day 3，Day 7
Lab test11	Total bilirubin IU/L	Day0，Day1，Day 3，Day 7
Lab test12	Cr μmol/L	Day0，Day1，Day 3，Day 7
Lab test13	IL-1βng/ml	Day0，Day1，Day 3，Day 7
Lab test14	APTT s	Day0，Day1，Day 3，Day 7
Lab test15	D-Dimermg/L	Day0，Day1，Day 3，Day 7
Lab test16	CRP mg/L	Day0，Day1，Day 3，Day 7
Lab test17	ProBNP pg/ml	Day0，Day1，Day 3，Day 7
Lab test18	PCT ng/ml	Day0，Day1，Day 3，Day 7
Lab test19	TNFαng/ml	Day0，Day1，Day 3，Day 7
Lab test20	IL-6 ng/ml	Day0，Day1，Day 3，Day 7

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Wu Jieping Medical Foundation
• Investigators: Study Director: Hongping Qu, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital

Publications and helpful links

General Publications

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19 Suppl 3(Suppl 3):S8. doi: 10.1186/cc14726. Epub 2015 Dec 18.
• Gutterman DD, Chabowski DS, Kadlec AO, Durand MJ, Freed JK, Ait-Aissa K, Beyer AM. The Human Microcirculation: Regulation of Flow and Beyond. Circ Res. 2016 Jan 8;118(1):157-72. doi: 10.1161/CIRCRESAHA.115.305364.
• Tian R, Wang X, Pan T, Li R, Wang J, Liu Z, Chen E, Mao E, Tan R, Chen Y, Liu J, Qu H. Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock. Scand J Immunol. 2019 Dec;90(6):e12823. doi: 10.1111/sji.12823. Epub 2019 Oct 7.
• Tian R, Li R, Liu Y, Liu J, Pan T, Zhang R, Liu B, Chen E, Tang Y, Qu H. Metformin ameliorates endotoxemia-induced endothelial pro-inflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1701-1712. doi: 10.1016/j.bbadis.2019.04.009. Epub 2019 Apr 16.
• Yao B, Liu DW, Chai WZ, Wang XT, Zhang HM. Microcirculation dysfunction in endotoxic shock rabbits is associated with impaired S-nitrosohemoglobin-mediated nitric oxide release from red blood cells: a preliminary study. Intensive Care Med Exp. 2019 Jan 7;7(1):1. doi: 10.1186/s40635-018-0215-0.
• Otero RM, Nguyen HB, Huang DT, Gaieski DF, Goyal M, Gunnerson KJ, Trzeciak S, Sherwin R, Holthaus CV, Osborn T, Rivers EP. Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest. 2006 Nov;130(5):1579-95. doi: 10.1378/chest.130.5.1579.
• Fan KL, Wang JH, Kong L, Zhang FH, Hao H, Zhao H, Tian ZY, Yin MX, Fang H, Yang HH, Liu Y. Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients. Chin J Integr Med. 2019 Jan;25(1):59-63. doi: 10.1007/s11655-017-2965-z. Epub 2017 Oct 6.
• Zhang XJ, Song L, Zhou ZG, Wang XM. Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury. World J Gastroenterol. 2006 Jul 21;12(27):4389-91. doi: 10.3748/wjg.v12.i27.4389.
• Zhang X, Guo T, Zhang K, Guo W, An X, Gao P. Effect of shenfu injection on microcirculation in shock patients: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020 Oct 23;99(43):e22872. doi: 10.1097/MD.0000000000022872.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Estimated): December 5, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: microcirculation; sepsis; Shenfu Injection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Anti-Bacterial Agents; Norepinephrine
• Other Study ID Numbers: 320.6750.2022-2-35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No